Kinins as Therapeutic Agents in Cardiovascular and Renal Diseases

Francois      Alhenc-Gelas; Nadine      Bouby; Christine      Richer; Louis      Potier; Ronan      Roussel; Michel      Marre

Abstract

A fair amount of data indicates that bradykinin and lysyl-bradykinin exert arterial, cardiac and renal effects which afford protection against organ damage in diseases, especially in the settings of ischemia or diabetes. The concept of kinins acting as therapeutic agents is supported by the wide use of angiotensin I-converting enzyme (ACE) inhibitors. These inhibitors indeed potentiate kinin action by inhibiting kinin degradation. Experimental evidence strongly suggests that the cardiac and renal effects of ACE inhibitors are due, at least in part, to kinins. Angiotensin AT1 receptor antagonists act also partly through kinins. This paper reviews available evidence supporting a role for kinins in the therapeutic effect of current drugs. It then discusses the opportunity to develop new drugs based on kinin action. Direct activation of the kinin B2 receptor by pharmacological agonists might provide higher therapeutic benefit than existing kinin- potentiating drugs. Possible occurrence of side effects is however a concern.

Keywords: Bradykinin, kinin receptors, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, kinin receptor agonists, cardiovascular diseases, cardiac ischemia, diabetic nephropathy, vascular endothelial cells, kallikrein-kinin systems